A Marfan syndrome gene expression phenotype in cultured skin fibroblasts

<p>Abstract</p> <p>Background</p> <p>Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms.</p> <p>Results</p> <p>We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR.</p> <p>Conclusion</p> <p>Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 × 10^-6under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater.</p

A Marfan syndrome gene expression phenotype in cultured skin fibroblasts-0

<p><b>Copyright information:</b></p><p>Taken from "A Marfan syndrome gene expression phenotype in cultured skin fibroblasts"</p><p>http://www.biomedcentral.com/1471-2164/8/319</p><p>BMC Genomics 2007;8():319-319.</p><p>Published online 12 Sep 2007</p><p>PMCID:PMC2174953.</p><p></p>qRT-PCR. Above each gene name are two "box-and-whisker" plots of expression levels for that gene across 32 unaffected control (UC) samples (left plot of each pair, blue, up-triangles) and 42 MFS affected samples (right, red, down-triangles). Vertical axis is logratio of expression level to the median UC level. Each "box" shows the inter-quartile range (IQR), i.e., the range between the 25and 75percentiles of the log ratios; the horizontal line in each box is the 50th percentile (median). (Median log ratio for UC is always zero, by definition.) "Whiskers" (vertical lines) extend from each box to the most extreme values within 1.5 times the IQR from the box; in normally distributed data this would on average encompass 99% of the values. Triangles mark more extreme points. The lower curve shows log(p-value) for a Wilcoxon rank sum test of the null hypothesis that the UC and MFS distribution are identical; horizontal line marks the p = 0.05 significance level. 6 of 10 genes have p-values < 0.05 by this test. Most genes exhibit noticeably greater variability across the MFS samples than across UC samples, although the Wilcoxon test is not sensitive to this. To highlight one example, for Elastin (), the middle 50% of the UC sample log ratios fall between -0.23 and +0.14 (i.e., the 25and 75percentiles of the values fall 1.70-fold below and 1.38-fold above the median, respectively), and all but 4 fall between -0.58 and +0.34 (4-fold below and 2.2-fold above median). In contrast, median Elastin level is 26 fold lower in MFS samples, only four MFS samples are above the UC median, and the null hypothesis has a p-value of 1.6 × 10